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RELYUBL SIGNED

Regulation of lymphocyte biology by ubiquitin and ubiquitin like modifiers

Total Cost €

0

EC-Contrib. €

0

Partnership

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 RELYUBL project word cloud

Explore the words cloud of the RELYUBL project. It provides you a very rough idea of what is the project "RELYUBL" about.

complexity    daunting    autoimmunity    immunity    disrupted    deterred    hence    differentiation    immune    activation    fundamentally    insights    ubls    components    roles    progress    protect    vivo    focussing    cell    ub    hypothesize    undiscovered    inflammation    remove    unknown    seeking    lymphocytes    malignant    ubiquitin       deregulation    disease    ubl    regulating    modules    tightly    substantial    cells    recognition    biology    biochemical    modifiers    proteome    regulated    area    intense    therapies    systematically    elucidate    networks    genetic    immunological    dependent    dynamic    signalling    implied    reveal    pathogens    focussed    adaptive    ultimately    full    ubiquitylation    severe    phosphorylation    tackled    protein    predominantly    modifications    give    disorders    regulate    ptms    pioneer    posttranslational    limited    discover    enzymes    mechanistic    rewriting    lymphocyte    modified    inform    lymphomas    proteins    nodes    mice    function    events   

Project "RELYUBL" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF DUNDEE 

Organization address
address: Nethergate
city: DUNDEE
postcode: DD1 4HN
website: www.dundee.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙499˙987 €
 EC max contribution 1˙499˙987 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF DUNDEE UK (DUNDEE) coordinator 1˙499˙987.00

Map

 Project objective

T lymphocytes are key cells of the adaptive immune system that protect us against pathogens and malignant cells. T cell activation and differentiation are tightly controlled processes and deregulation can result in lymphomas, autoimmunity and inflammation. Hence, the biochemical events regulating lymphocyte biology have long been a topic of intense research, which has been focussed predominantly on protein phosphorylation. I hypothesize that there are crucial roles undiscovered in T cells for other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like proteins (UBLs). The importance of ubiquitylation in adaptive immunity is implied by the severe immunological disorders observed when components of the Ub system are disrupted in lymphocytes. Genetic approaches in mice give a limited understanding about the roles of these modifiers and do not reveal the full extent to which Ub and UBLs regulate lymphocyte biology. Deterred by the complexity of the Ub system, the field has not yet tackled the daunting challenge of systematically investigating these modifiers in vivo. The goal of this proposal is to define how T cell function and immune responses are regulated by Ub and UBL signalling networks. To pioneer substantial progress in this area, we will develop new methods to identify and characterize currently unknown recognition modules for the different modifications. We will elucidate the Ub and UBL modified proteome in lymphocytes and characterize dynamic changes of these PTMs during T cell activation. By focussing on enzymes that remove the modifications we will discover how these PTMs are regulated and define Ub and UBL-dependent signalling nodes. Each phase of the work will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease.

 Publications

year authors and title journal last update
List of publications.
2018 Dominika Kwasna, Syed Arif Abdul Rehman, Jayaprakash Natarajan, Stephen Matthews, Ross Madden, Virginia De Cesare, Simone Weidlich, Satpal Virdee, Ivan Ahel, Ian Gibbs-Seymour, Yogesh Kulathu
Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability
published pages: 150-164.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.02.023
Molecular Cell 70/1 2019-05-01

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